PMID- 20195281 OWN - NLM STAT- MEDLINE DCOM- 20110308 LR - 20180822 IS - 1440-1711 (Electronic) IS - 0818-9641 (Linking) VI - 88 IP - 6 DP - 2010 Aug TI - Cross-presentation of HCMV chimeric protein enables generation and measurement of polyclonal T cells. PG - 676-84 LID - 10.1038/icb.2010.20 [doi] AB - CD8(+) T cell immunity has a critical function in controlling human cytomegalovirus (HCMV) infection. In immunocompromized individuals, HCMV reactivation or disease can lead to increased morbidity and mortality, particularly in transplant recipients. In this setting, adoptive transfer of HCMV-specific CD8(+) T cells is a promising vaccine strategy to restore viral immunity, with most clinical approaches focussing on the use of peptides for the generation of single epitope-specific CD8(+) T cells. We show that using an IE1-pp65 chimeric protein as the antigen source promotes effective cross-presentation, by monocyte-derived dendritic cells (MoDCs), to generate polyclonal CD8(+) T cell epitopes. By exploring human leukocyte antigen (HLA)-restricted immunodominance hierarchies both within and across two immunodominant proteins, we show that HLA-B7 epitopes elicit higher CD8(+) T cell responses compared with HLA-A1, -A2 or -B8. This study provides important evidence highlighting both the efficacy of the IE1-pp65 chimeric protein and the importance of immunodominance in designing future therapeutic vaccines. FAU - Nguyen, Thi H O AU - Nguyen TH AD - Malignant Haematology and Stem Cell Transplantation Service, The Alfred Hospital, Victoria, Australia. FAU - Sullivan, Lucy C AU - Sullivan LC FAU - Kotsimbos, Tom C AU - Kotsimbos TC FAU - Schwarer, Anthony P AU - Schwarer AP FAU - Mifsud, Nicole A AU - Mifsud NA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100302 PL - United States TA - Immunol Cell Biol JT - Immunology and cell biology JID - 8706300 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA Antigens) RN - 0 (IE1-pp65 recombinant protein, Human cytomegalovirus) RN - 0 (Immediate-Early Proteins) RN - 0 (Immunodominant Epitopes) RN - 0 (Phosphoproteins) RN - 0 (Recombinant Proteins) RN - 0 (Viral Matrix Proteins) SB - IM MH - CD8-Positive T-Lymphocytes/immunology/*metabolism/pathology MH - Cross-Priming MH - Cytomegalovirus/*immunology/pathogenicity MH - Cytomegalovirus Infections/*immunology/therapy/virology MH - Dendritic Cells/immunology/*metabolism/pathology MH - Epitopes, T-Lymphocyte/genetics/*metabolism MH - HLA Antigens/immunology/metabolism MH - Humans MH - Immediate-Early Proteins/genetics/immunology/*metabolism MH - Immunodominant Epitopes/genetics/*metabolism MH - *Immunotherapy, Adoptive MH - Lymphocyte Activation MH - Monocytes/pathology MH - Phosphoproteins/genetics/immunology/*metabolism MH - Protein Binding/immunology MH - Recombinant Proteins/genetics/immunology/metabolism MH - Viral Matrix Proteins/genetics/immunology/*metabolism MH - Virus Activation EDAT- 2010/03/03 06:00 MHDA- 2011/03/09 06:00 CRDT- 2010/03/03 06:00 PHST- 2010/03/03 06:00 [entrez] PHST- 2010/03/03 06:00 [pubmed] PHST- 2011/03/09 06:00 [medline] AID - icb201020 [pii] AID - 10.1038/icb.2010.20 [doi] PST - ppublish SO - Immunol Cell Biol. 2010 Aug;88(6):676-84. doi: 10.1038/icb.2010.20. Epub 2010 Mar 2.